Obesity and its co-morbidities continue to be a growing problem in this country. This is particularly so in African Americans and within this group, in women. Insulin resistance is one co-morbidity associated with obesity and is found to a greater degree in African Americans compared to Caucasians. Intramyocellular Lipids (IMCL- the fat within the myocytes) have been shown to be inversely related to a person's insulin sensitivity (SI). To date, it is not known if racial differences exist in IMCL content or whether it plays a role in the increased insulin resistance in African Americans. We have shown that African American women have increased skeletal muscle volume. The skeletal muscle in African American women may have a greater amount of IMCL, which can explain the greater degree of insulin resistance. We propose to explore aspects of muscle physiology and metabolism to identify if racial differences exist 1) in IMCL content and how this relates to SI; 2) in IMCL content and SI response to manipulations of fat and carbohydrate content of eucaloric diets. To answer these questions we propose to study lean and obese, pre-menopausal, non- diabetic African Americans and Caucasians women using 1) proton magnetic resonance spectroscopy (1H MRS) at baseline and after low and high fat diets, 2) frequently sampled intravenous glucose tolerance test at baseline and 3) hyperinsulinemic-euglycemic clamps after low and high fat diets. These studies will help in the understanding of the mechanisms of increased insulin resistance in the African American population. This is an important public health problem and results arising from the proposed studies may to lead to the development of new approaches for the treatment of this condition and prevention of related illnesses such as type 2 diabetes in African Americans. In this regard these studies may help to identify mechanisms for race-ethnic disparities in the incidence of type 2 diabetes mellitus and therefore respond to the NIH PA number 04-074. [unreadable] [unreadable] [unreadable]